Applications Vaccixcell

Lentivirus

A study was made in 2016 about Production of lentiviral vectors and it showed that Lentiviral vectors (LV) have seen considerably increase in use as gene therapy vectors for the treatment of acquired and inherited diseases. This evaluation presents the state of the art of the production of these vectors with particular emphasis on their large-scale production for clinical purposes. In contrast to oncoretroviral vectors, which are produced using stable producer cell lines, clinical-grade LV are in most of the cases produced by transient transfection of HEK 293T cells grown in cell factories.

Since the human body is an extraordinary machine, most of the time T-cells from your immune system can identify and kill naturally occurring cancer cells. But cancer cells are robust and can develop strategies to evade or deceive the immune system, making your T-cells ineffective and therefore leading to the development of a tumor. To enhance the ability of the immune system to identify cancer cells, engineered Chimeric Antigen Receptors (CAR) can be expressed on the surface of the T-cells, providing them with a specific cancer targeting mechanism. CAR + T-Cell = CAR-T

The first step consists of harvesting the T-cells from the patient (autologous therapy) or from a healthy person (allogeneic therapy). Then transfect these cells via a vector to give them a new sequence of DNA which codes for the new receptor CAR. Once back in the body, the engineered T-cells will express the receptors on their surface, duplicate and then flow through your body to detect and attack the cancer cells. Another advantage of this therapy is the long-term effects due to the 'memory' of your immune system.

To engineer the T-cells, scientists need to go inside the cell to genetically modify its DNA genome. This is a key step, because T-cells are very refractory to the entry of foreign DNA, consequently scientists need a very efficient gene transfer tool. Currently, the most efficient way to go inside T-cells is the use of Lentiviral Vectors. These viruses are made of an envelope, a capsid and, inside, a RNA genome. The lentiviruses enter in their target cells with a very high efficiency. Once inside the cell, RNA genome is reverse-transcribed in DNA and is integrated into the genome of the cell thanks to the viral integrase enzyme. The idea is to utilize these interesting natural biological properties to serve as an efficient gene transfer tool. To this end, the genes required for the viral replication and inducing pathogenic effects are replaced by genes of interest, for example CAR.T-cells are now supercharged against cancer.

 

Esco VacciXcell Advantage

Esco Vaccixcell tidemotion bioreactors, CelCradle™ and TideXcell are proven systems in culturing adherent cells such as HEK293. Our patented tidemotion technology along with proprietary BioNOC II macrocarriers ensures that the cells attach and stays attach during inoculation and culture process. The gentle tidemotion provides unlimited oxygenation and nutrion while virtually eliminating shear stress. Being the only TRUE LINEARLY SCALABLE system, from 0.5 L to 5,000 L, in the market, Esco Vaccixcell's tidemotion bioreactor reduces cost, labor requirement and bioprocessing time.

Esco VacciXcell's Tide Motion System is the highest yield and lowest cost packed bed bioreactor system and the only packed bed bioreactor that can be placed inside a cGMP isolator, making it an ideal system for the production of wild-type viruses.

On top of this, Esco VacciXcell can provide turnkey solutions for the gene therapy industry, beginning from research and development, all the way to the production scale of the end product.

 

References:

Merten, O.-W., Hebben, M., & Bovolenta, C. (2016). Production of lentiviral vectors. , 3. Retrieved from www.ncbi.nlm.nih.gov :(Merten, Hebben, & Bovolenta, 2016)

Lentiviral vectors: the secret behind the rise of CAR-T therapies www.labiotech.eu